key: cord-294728-fefkvg0a
authors: Vick, Dan J.
title: GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY AND COVID-19 INFECTION
date: 2020-06-06
journal: Mayo Clin Proc
DOI: 10.1016/j.mayocp.2020.05.035
sha: 
doc_id: 294728
cord_uid: fefkvg0a

nan

To the Editor:

One unsettling aspect of the COVID-19 (SARS-CoV-2) pandemic is the variable susceptibility to infection. Some people who are exposed remain asymptomatic, others experience mild to moderate symptoms, while still others become severely ill and die.

Hospitalization rates increase with age and approximately 90% of hospitalized patients have underlying medical conditions. 1 However, this doesn't account for a number of otherwise healthy or younger patients who are severely affected. Other suggested factors include genetic determinants.

A condition that should be considered is glucose-6-phosphate dehydrogenase (G6PD) deficiency. This X-linked recessive disorder with numerous allelic variants affects some 400 million people worldwide, with higher prevalence in Africa, the Mediterranean region, and Asia.

Decreased production of G6PD results in deficient levels of NADPH and reduced glutathione, causing oxidative stress and red blood cell destruction. Although frequently asymptomatic, patients may develop hemolytic anemia triggered by certain infectious agents and medications. 2 There is evidence to suggest an association between G6PD deficiency and increased susceptibility to, and severity of illness with, COVID-19 infection.

Wu et al. 3 found that G6PD deficiency enhanced infection of cells with coronavirus 229E (HCoV 229E). Using G6PD-deficient fibroblasts and G6PD-knockdown cells derived from human lung epithelial cells subjected to viral inoculum in vitro, they found that viral gene expression was higher in these cells compared with control cells. Production of viral particles in the deficient cells was also higher over time, indicating that G6PD activity modulates this production. Further, the G6PD deficient cells were more susceptible to HCoV 229E mediated cell death. SARS-CoV-2 may have a similar effect on cells in G6PD deficient patients.

Spain and Italy have been particularly affected by the COVID-19 pandemic, with case fatality rates of 12.0% and 14.2%, respectively, as of this writing. 4 G6PD deficiency is more common in the Mediterranean region. On the Italian island of Sardinia alone, the prevalence ranges from 10% to 15%. 5 The allelic variants of G6PD deficiency in the Mediterranean region tend to manifest more significant phenotypic presentations. Although other factors may account for severity of illness in these countries, G6PD deficiency should be considered.

Reports from the United Kingdom and the United States show increased numbers of COVID-19 infection among members of minority groups. In the U.K., 63% of the first 106 health care and social workers who died from the virus were black, Asian, or minority ethnic (BAME). BAME individuals make up 34% of patients admitted to U.K. ICUs, although they only account for 17% of the population in the U.K. 6 In the U.S., African Americans have been more significantly affected than other races. Yancy 7 noted the infection rate in 131 predominantly black counties is 137.5/100 000 and the death rate is 6.3/100 000. These rates are three times and six times higher, respectively, than what is found in mostly white counties. Preexisting medical conditions and adverse socioeconomic determinants of health may explain some of this disparity. However, G6PD deficiency is common among blacks and Asians. In a study of 63,302 U.S. military personnel, 2.5% of males and 1.6% of females overall were deficient.

Prevalence was higher among African American males (12.2%) and females (4.1%), as well as Asian males (4.3%). 8 G6PD deficiency may play a role in COVID-19 severity of illness and death in these groups.

Vascular endothelial dysfunction and coagulopathy have been suggested as complications of COVID-19, based on a report of large vessel ischemic stroke occurring in five U.S. patients under age 50, including two without preexisting conditions. Similar cases have occurred in China and Singapore. 9 Coagulopathy has also been observed in people with G6PD deficiency.

Albertsen et al 10 Chloroquine has infrequently been reported to cause hemolysis in G6PD deficient patients and caution is advised for its use. 11 Hydroxychloroquine, its molecular variant, is generally considered safe. Both antimalarial drugs are being trialed as possible treatments for COVID-19. However, a recent report described an acute hemolytic episode occurring in a COVID-19 patient with G6PD deficiency who was treated with hydroxychloroquine. 12 Hydroxychloroquine may increase the oxidative stress in COVID-19 patients with G6PD deficiency, thereby serving as a trigger for hemolytic anemia.

Studies are needed to determine whether a positive correlation exists between G6PD deficiency and COVID-19, with respect to increased susceptibility to infection and severity of illness. This is important for several reasons. First, it will allow for identification of a subset of COVID-19 patients for whom close monitoring and supportive care may be critical. Second, certain treatments, such as hydroxychloroquine, may be contraindicated in these patients. Third, identification of this relationship may suggest other therapies, such as use of antioxidants, that may prove beneficial for treating COVID-19. Finally, such information will be important for people with known G6PD deficiency to guide their decisions and actions to prevent COVID-19 infection.

Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 -COVID-NET, 14 States

Glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase deficiency enhances human coronavirus 229E infection

COVID-19 dashboard

Glucose-6-phosphate dehydrogenase (G6PD) deficiency in nonarteritic anterior ischemic optic neuropathy in a Sardinian population

Exclusive: Deaths of NHS staff from covid-19 analysed

COVID-19 and African Americans

Prevalence of glucose-6-phosphate dehydrogenase deficiency in U.S. Army personnel

Large-vessel stroke as a presenting feature of Covid-19 in the young

Fatal haemolytic crisis with microvascular pulmonary obstruction mimicking a pulmonary embolism in a young African man with glucose-6-phosphate dehydrogenase deficiency

Haemoglobinopathies and G.-6-P.D. deficiency in Laos

Acute hemolysis by hydroxychloroquine was observed in G6PD-deficient patient with severe COVID-19 related lung injury